期刊
JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
卷 120, 期 1, 页码 492-501出版社
ACOUSTICAL SOC AMER AMER INST PHYSICS
DOI: 10.1121/1.2205129
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资金
- NCI NIH HHS [R21-CA91166, R01-CA81512, R01 CA081512, R21 CA091166] Funding Source: Medline
- NIBIB NIH HHS [R01 EB002682-03, R01-EB02682, R01 EB002682, R01 EB002682-04] Funding Source: Medline
In this work, the activation of heat-sensitive trans-gene by high-intensity focused ultrasound (HIFU) in a tumor model was investigated. 4T1 cancer cells (2 x 10(6)) were inoculated subcutaneously in the hind limbs of Balb/C mice. The tumors were subsequently transducted on day 10 by intratumoral injection of a heat-sensitive adenovirus vector (Adeno-hsp70B-Luc at 2 x 10(8) pfu/tumor). On day 11, the tumors were heated to a peak temperature of 55, 65, 75, or 85 degrees C within 10-30 s at multiple sites around the center of the tumor by a 1.1- or 3.3-MHz HIFU transducer. Inducible luciferase gene expression was increased from 15-fold to 120-fold of the control group following 1.1-MHz HIFU exposure. Maximum gene activation (120-fold) was produced at a peak temperature of 6575 degrees C one day following HIFU exposure and decayed to baseline within 7 days. HIFU-induced gene activation (75 degrees C-10 s) could be further improved by using a 3.3-MHz transducer and a dense scan strategy to 170-fold. Thermal stress, rather than nonthermal mechanical stress, was identified as the primary physical mechanism for HIFU-induced gene activation in vivo. Overall, these observations open up the possibility for combining HIFU thermal ablation with heat-regulated gene therapy for cancer treatment. (c) 2006 Acoustical Society of America.
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